PROJECT SUMMARY Prostate cancer is the leading cause of cancer prevalence and incidence in men worldwide. In the United States, alone, nearly 3 million prevalent cases and approximately 180,000 new cases of prostate cancer are expected to occur in the year 2016. Although many men will be diagnosed with prostate cancer, most deaths from prostate cancer occur in men who develop advanced-stage disease. Unfortunately, knowing who will progress to advanced-stage disease remains a significant medical challenge, as risk factors for prostate cancer progression are not well understood. Depression, however, may be one such risk factor. Previous research has shown that depression (1) is highly prevalent among men diagnosed with early-stage prostate cancer, (2) may share some of the same proposed biological mechanisms with prostate cancer progression, (3) is associated with behavioral changes that can increase one?s risk for adverse health outcomes and (4) treatment may lessen some of the negative consequences of depression in individuals with cancer, including the possible increased risk of cancer progression. Therefore, the goal of the present investigation is to test the hypothesis that men diagnosed with clinical depression and early-stage prostate cancer are at an increased risk for both biochemical progression and the development of advanced-stage disease and that depression treatment, through antidepressant medication use and/or depression psychotherapy, will mitigate this increased risk. Utilizing electronic health record data, from the nearly 36,000 male-members of the Kaiser Permanente Southern California integrated healthcare system diagnosed with early-stage prostate cancer between 2000 and 2014, we will (1) test whether a diagnosis of depression (without depression treatment) is associated with prostate cancer biochemical progression and/or the development of advanced-stage prostate cancer after controlling for identified socio-demographic, health history and clinical characteristic confounders and (2) further evaluate whether (i) antidepressant medication use, (ii) depression psychotherapy and/or (iii) antidepressant medication use with depression psychotherapy (all with and without a depression diagnosis) is associated with prostate cancer biochemical progression and/or the development of advanced-stage prostate cancer after controlling for identified socio-demographic, health history and clinical characteristic confounders. Findings from this investigation could benefit men with early-stage prostate cancer by (1) providing insight into the possible risk of prostate cancer progression in men with comorbid depression, (2) highlighting potential disparities in depression burden by clinical and/or socio-demographic factors, (3) creating evidence to advocate for increased care-coordination within the current healthcare delivery and depression management models, (4) identifying men who could benefit most from increased depression screening or psychosocial intervention leading to tailored future psychosocial interventions and (5) advocating for the conduct of further investigations into the possible relationship between depression and prostate cancer progression.